Genetic approaches and the identification of candidate genes in the mouse can aid in the discovery of mutations responsible for human AHL (age-related hearing loss), which is a very heterogenous and common type of deafness. The preliminary studies of the present research profiled the cochlear gene expression in two mouse models of AHL in simultaneous hybridization experiments using commercially available mouse cDNA expression arrays. With this approach, several RNA transcripts that were expressed at distinctly different levels were identified. It is the goal of the proposed project to investigate more thoroughly the relevance of these molecules to AHL. The first specific aim is to confirm which of the candidate transcripts identified using the mouse cDNA array experiments are expressed at significantly different levels in the cochlea of C57 and CBA mice, which have previously been shown to exhibit distinctive early- and late-onset AHL. Cochlear RNA from CBA and C57 mice will be tested using both relative RT-PCR techniques, and RNase protection assays. The second specific aim will use in situ hybridization techniques to identify which cell types in the mouse cochlea express each one of the candidate transcripts thought to play important roles in the pathological mechanisms associated with AHL. Together, these goals are aimed at confirming the relevance of these molecules to AHL. In this manner, new avenues of productive research may be opened up to the elucidation of mechanisms that cause hearing loss.